Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells

Kai Wang, Anthony K. Guzman, Zi Yan, Shouping Zhang, Michael Y. Hu, Mehdi B. Hamaneh, Yi Kuo Yu, Seda Tolu, Jinghang Zhang, Holly E. Kanavy, Kenny Ye, Boris Bartholdy, Eric E. Bouhassira

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Efficiency of reprogramming of human cells into induced pluripotent stem cells (iPSCs) has remained low. We report that individual adult human CD49f + long-term hematopoietic stem cells (LT-HSCs) can be reprogrammed into iPSCs at close to 50% efficiency using Sendai virus transduction. This exquisite sensitivity to reprogramming is specific to LT-HSCs, since it progressively decreases in committed progenitors. LT-HSC reprogramming can follow multiple paths and is most efficient when transduction is performed after the cells have exited G 0 . Sequencing of 75 paired skin fibroblasts/LT-HSC samples collected from nine individuals revealed that LT-HSCs contain a lower load of somatic single-nucleotide variants (SNVs) and indels than skin fibroblasts and accumulate about 12 SNVs/year. Mutation analysis revealed that LT-HSCs and fibroblasts have very different somatic mutation signatures and that somatic mutations in iPSCs generally exist prior to reprogramming. LT-HSCs may become the preferred cell source for the production of clinical-grade iPSCs.

Original languageEnglish (US)
Pages (from-to)2580-2592.e7
JournalCell Reports
Volume26
Issue number10
DOIs
StatePublished - Mar 5 2019

Fingerprint

Induced Pluripotent Stem Cells
Hematopoietic Stem Cells
Stem cells
Fibroblasts
Mutation
Nucleotides
Sendai virus
Skin
Viruses
Cells

Keywords

  • induced pluripotent stem cells
  • long-term hematopoietic stem cells
  • reprogramming
  • skin fibroblasts
  • somatic mutation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells. / Wang, Kai; Guzman, Anthony K.; Yan, Zi; Zhang, Shouping; Hu, Michael Y.; Hamaneh, Mehdi B.; Yu, Yi Kuo; Tolu, Seda; Zhang, Jinghang; Kanavy, Holly E.; Ye, Kenny; Bartholdy, Boris; Bouhassira, Eric E.

In: Cell Reports, Vol. 26, No. 10, 05.03.2019, p. 2580-2592.e7.

Research output: Contribution to journalArticle

Wang, Kai ; Guzman, Anthony K. ; Yan, Zi ; Zhang, Shouping ; Hu, Michael Y. ; Hamaneh, Mehdi B. ; Yu, Yi Kuo ; Tolu, Seda ; Zhang, Jinghang ; Kanavy, Holly E. ; Ye, Kenny ; Bartholdy, Boris ; Bouhassira, Eric E. / Ultra-High-Frequency Reprogramming of Individual Long-Term Hematopoietic Stem Cells Yields Low Somatic Variant Induced Pluripotent Stem Cells. In: Cell Reports. 2019 ; Vol. 26, No. 10. pp. 2580-2592.e7.
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